Project IV. Neuroimaging of Social Brain Circuitry This project builds on prior results to better characterize the neural substrate of WS, and in particular the structural and neurophysiological characteristics that may underlie its striking social phenotype. Our first aim focuses on structural changes in WS, utilizing comprehensive, validated, automated and quantitative analyses of MRI and DTI, based on segmentation of the cerebral volume, reconstruction and parcellation of the cortical surface, and tractography of the white matter. In addition to confirming previous results (such as increased amygdala volume) with different techniques in an independent population of WS, we will test hypotheses derived from previous behavioral and functional imaging results, suggesting changes in the posterior fusiform and anteroventral temporal, subgenual, orbital and anterior insular cortices. We will also quantify the fiber tracts connecting the amygdala to ventral prefrontal and fusiform face areas. Our second aim examines the functional bases of sociability changes in WS using magnetoencephalography (MEG). Anatomically-constrained distributed procedures will estimate cortical activation patterns with excellent temporal and good spatial accuracies. We will test the hypothesized neural substrates for the sensitivity of WS to faces compared to control stimuli, and especially to happy compared to sad faces. The strength and direction of functional communication between different parts of the system processing facial emotions will be examined with event-related spectral measures. In the third aim, we will examine the inter-relation of structural, functional and genetic bases of sociability in WS. For example, we will test if face-selective MEG responses correlate with fusiform structural measures, emotional with amygdala and its connections in orbital, ventral, medial and opercular prefrontal cortices. In addition, we will test if the ERP and psychophysical data from Project 5 correlate with specific structural measures, and compare our anatomical results with direct histological examination of the same locations in Project 3. In summary, this project aims to identify anatomical and physiological circuits linking the genetic deletion to the social-behavioral RELEVANCE (See instructions): These studies may help identify the neural circuits underlying specific social behaviors in WS, and thus by extension, in the healthy population. In addition to the specific application of these studies to WS, a relatively common source of genetically-caused retardation, these insights may contribute to the neurobiological understanding necessary to design biological treatments for neuropsychiatric disorders of social behavior.